Method for the production of alkyllithium compounds by using reduced pressure

ABSTRACT

Disclosed is a method for producing Alkyllithium compounds by reacting metallic lithium with an Alkyl halide in a solvent. The reaction is performed at a reduced pressure at the boiling point of the solvent.

The invention concerns a process for the production of alkyl lithiumcompounds under reduced pressure.

Alkyl lithium compounds are produced by reacting organic halogencompounds with metallic lithium. The reaction is conventionallyperformed in hydrocarbons or in ethers as solvent.

WO 95/01982 provides a detailed description of the production of alkyllithium compounds from lithium metal dispersion and alkyl halide,mentioning the sodium content of the lithium, the lithium excessrelative to the alkyl halide, the alkyl halide, the metering rate, thesolvent, the influence of the traces of water in the reaction and thereaction temperature. Depending on the solvent used, the reactionbetween lithium and alkyl halide is performed at the boiling point ofthe solvent between 50 and 100° C., or between 50 and 125° C. below theboiling point of the solvent.

WO 96/40692 describes a process for the production of lithium-organicsolutions, wherein cast or extruded lithium rods react with an alkylhalide (e.g. n-, s- or t-butyl chloride) in a molar excess of 3:1 to20:1 in a solvent under a protective gas atmosphere for 1 to 10 hourswith moderate stirring, and the product is separated from lithium metaland the secondary product LiCl in the reactor. In a variant of theprocess likewise described in WO 96/40692, stirring is not performedduring the reaction (the LiCl formed remains on the Li metal), theproduct solution is separated off, and after separating off the LiCl(e.g. by adding solvent, stirring and separating off the LiClsuspension) the excess Li metal together with newly added metal isreacted again with added alkyl halide in the replenished solvent.

The reaction of lithium with an alkyl halide is a highly exothermicreaction. The lithium is generally placed in the solvent and the alkylhalide metered in at the rate at which the reaction heat can bedissipated. In the production of n-butyl lithium in hexane, for example,the temperature increases rapidly from room temperature (20° C.) to theboiling point of hexane (68° C.). The reaction heat that is released canbe dissipated through the reactor jacket or by evaporative cooling ofthe solvent (utilising the enthalpy of vaporisation of the solvent).

To achieve as rapid and complete a reaction as possible, an elevatedtemperature can in principle be chosen for the reaction of Li metal withalkyl halides, particularly alkyl chlorides, e.g. the boilingtemperature of common solvents such as hexane (68° C.) or heptane (98°C.). Unfortunately this is not always practical, however, since anelevated temperature has a negative effect-on the yield. Thus atelevated temperatures there is an increased occurrence of undesirableWurtz reactions, thermal degradation of the alkyl lithium compounds andother secondary reactions. In the case of butyl lithium compounds,s-butyl lithium displays greater thermal sensitivity than n-butyllithium. Isobutyl lithium displays especially high thermal sensitivity.In the case of n-alkyl lithium compounds, the aforementioned undesirablereactions occur in particular with synthesis in higher-boiling solventsthan hexane such as heptane (a preferred solvent for alkyl lithiumcompounds) or octane. In the case of branched s- and t-alkyl lithiumcompounds this can be observed even at temperatures below the boilingpoint of hexane (68° C.). For these reasons t-butyl lithium, forexample, is generally produced in boiling pentane at a temperature ofonly 33° C. If on the other hand the synthesis of alkyl lithiumcompounds is performed below the solvent boiling point, the scale of theundesirable secondary reactions is smaller because of the lowertemperature, but the reaction is often retarded and accumulation of thealkyl halide can easily occur as a consequence, which in turn can allowthe reaction to go out of control.

The object of the invention is to overcome the disadvantages of theprior art and to provide a process for the production of alkyl lithiumcompounds that allows as high as possible a reaction rate with highyields, without the occurrence of undesirable secondary reactions.

The object is achieved by a process in which metallic lithium is reactedwith an alkyl halide in a solvent, wherein the reaction is performedunder reduced pressure and at the boiling point of the solvent. “Reducedpressure” should be understood to mean that the pressure in the reactionvessel is below the ambient pressure (atmospheric pressure).

Although in this mode of reaction the reaction temperatures are belowthe boiling points under normal pressure of the solvents used, theparticularly preferred reaction temperatures being 25 to 50° C., forexample, the yield when the process is performed at reduced pressure issignificantly higher than in a comparable reaction that is performed atthe same temperature but under normal pressure. The reason for this maybe that the boiling solvent forms vapour bubbles on the surface of thelithium, which make it easier for the LiCl that is formed to be detachedfrom the Li metal surface.

Depending on the chosen solvent, the reaction is preferably performedunder a pressure of 10 to 900 mbar, particularly preferably 50 to 500mbar. Preferred temperatures are 0 to 80° C., particularly preferredtemperatures 20 to 50° C.

An advantage of the process according to the invention is that whenlithium is reacted with an alkyl halide in a solvent, a high and uniformreaction rate is achieved and at the same time secondary reactions areeffectively suppressed because of the relatively low temperature. Thisapplies in particular for more thermolabile alkyl lithium compounds,e.g. sec- and tert-butyl lithium and especially also isobutyl lithium.In addition, with the aid of the process according to the invention thereaction can be performed in higher-boiling solvents (e.g. cyclopentane,cyclohexane, methyl cyclohexane, heptane, octane, nonane, decane,toluene, ethyl benzene or mesitylene). Thus solutions of alkyl lithiumcompounds can be prepared in higher-boiling solvents without the needfor a solvent exchange, as was previously the case. Another advantage isthat the previously common use of ethers as solvent or solvent component(ethers serve to release Li halides from the Li surface) can be avoided.A further advantage of the process according to the invention is thatbutyl lithium can be synthesised in aromatic hydrocarbons such astoluene, for example, without this resulting in a metallisation of thearomatics.

As the reaction is performed according to the invention at the boilingpoint of the particular solvent, the reaction heat formed canadvantageously be dissipated through the enthalpy of vaporisation of thesolvent, which represents an advantage over the jacket cooling that isotherwise performed in reactions below the solvent boiling point.

The invention is described in more detail below by reference toexamples.

EXAMPLE 1 Production of s-butyl Lithium in Cyclohexane at 40° C. underVacuum

24.5 g of Li powder (3.60 mol) were stirred with 0.5 g of LiH powder in100 ml of cyclohexane for 30 minutes at room temperature and thereaction initiated by the addition of 2 ml of s-butyl chloride.

A further 570 ml of cyclohexane (in total 500 g=670 ml) were added andthe reaction was again initiated with 5 ml of s-butyl chloride.Following a temperature rise (reaction kick-off) the internaltemperature was adjusted to 40° C. and the pressure reduced until thesolvent came to the boil (250 mbar). The remaining s-butyl chloride(total amount 138 g, 1.49 mol) was then added within 80 minutes and thereaction continued for a further 60 minutes. The vacuum was thenreleased with argon, the reaction mixture cooled to room temperature andfiltered, and washed with cyclohexane.

663 g of a clear, almost colourless solution were obtained with 2.24mmol of s-butyl lithium per g of solution.

Total amount of s-butyl lithium 1.49 mol (>99% yield).

COMPARATIVE EXAMPLE A Production of s-butyl Lithium in Cyclohexane at81° C. under Normal Pressure

In analogy to example 1, 10.0 g of Li powder (1.44 mol) were reacted in253 g of cyclohexane with 40 g of s-butyl chloride within 1 hour, thereaction being performed in contrast to example 1 under normal pressureand the solvent boiling at 81° C. The reaction was continued for afurther 30 minutes. The reaction solution obtained had a total basecontent of 1.31 mmol per g of solution, which corresponds to a yield ofa maximum of 84.7%.

A comparison of the results from example 1 and comparative example Ashows that the yield from the performance of the process according tothe invention (reaction at reduced temperature but at boiling point dueto the vacuum) is significantly higher than that from the performance ofthe known process (reaction at elevated temperature at boiling pointunder normal pressure).

EXAMPLE 2 Production of t-butyl Lithium in Hexane at VariousTemperatures under Vacuum

21.0 g of Li powder (3.02 mol) were stirred with 0.1 g of LiH powder in100 ml of hexane for 30 minutes at room temperature and the reactioninitiated by addition of 2 ml of t-butyl chloride.

A further 700 ml of hexane (in total 535 g=800 ml) were added and thereaction was again initiated with 5 ml of t-butyl chloride. Following atemperature rise (reaction kick-off) the internal temperature wasadjusted to 50° C. and the pressure reduced until the solvent came tothe boil (500 mbar). The remaining t-butyl chloride (total amount 92.6g, 1 mol) was then added within 4 hours and the reaction continued for afurther 1 hour. The vacuum was then released with argon, the reactionmixture cooled to room temperature and filtered, and washed with hexane.

693 g of a clear solution were obtained with a content of 0.96 mmol oft-butyl lithium per g of solution, which corresponds to a yield of66.5%.

The reaction was performed in an analogous way at around 40° C. andunder 400 mbar. 691 g of a clear solution were obtained with a contentof 1.12 mmol of t-butyl lithium per g of solution, which corresponds toa yield of 77.4%.

The reaction was performed again in an analogous way at around 30° C.and under 300 mbar. 626 g of a clear solution were obtained with acontent of 1.53 mmol of t-butyl lithium per g of solution, whichcorresponds to a yield of 95.8%.

These 3 examples show the direct synthesis of t-butyl lithium in hexane.The previously conventional circuitous route via synthesis in pentanewith subsequent laborious solvent exchange can now be avoided with theprocess according to the invention. The increase in yield at lowertemperatures can also clearly be seen.

EXAMPLE 3 Production of n-butyl Lithium in Methyl Cyclohexane at 50° C.under Vacuum

22.3 g of Li powder (3.2 mol) were stirred with 0.3 g of LiH powder in100 ml of methyl cyclohexane for 30 minutes at room temperature and thereaction initiated by addition of 2 ml of n-butyl chloride.

A further 560 ml of hexane (in total 500 g=660 ml) were added and thereaction was again initiated with 2 ml of n-butyl chloride. Following atemperature rise the internal temperature was adjusted to 50° C. and thepressure reduced until the solvent came to the boil (190 mbar). 148.5 g(1.6 mol) of n-butyl chloride were then added within 120 minutes and thereaction continued for a further 30 minutes. The vacuum was thenreleased with argon, the reaction mixture cooled to room temperature andfiltered, and washed with methyl cyclohexane.

558 g of clear, colourless product solution were obtained with a contentof 2.46 mmol/g of n-butyl lithium and 127 g of wash filtrate with acontent of 0.76 mmol/g of n-butyl lithium. The isolated yield was 1.5mol (91.8%)

EXAMPLE 4 Production of n-butyl Lithium in Toluene at 50° C. underVacuum

22.3 g of Li powder (3.2 mol) were stirred with 0.3 g of LiH powder in100 ml of toluene for 30 minutes at room temperature and the reactioninitiated by addition of 2 ml of n-butyl chloride.

A further 485 ml of toluene (in total 500 g=585 ml) were added and againinitiated with 2 ml of n-butyl chloride. Following a temperature risethe internal temperature was adjusted to 50° C. and the pressure reduceduntil the solvent came to the boil (140 mbar). 148.5 g (1.6 mol) ofn-butyl chloride were then added within 120 minutes and the reactioncontinued for a further 30 minutes. The vacuum was then released withargon, the reaction mixture cooled to room temperature and filtered, andwashed with toluene.

532 g of a clear, colourless product solution were obtained with acontent of 2.45 mmol/g of n-butyl lithium and 133 g of wash filtratewith a content of 1.06 mmol/g of n-butyl lithium, which corresponds to ayield of 1.45 mol=90.3%.

1-6. (canceled)
 7. A process for the production of an alkyl lithiumcompound comprising reacting metallic lithium with an alkyl halide in asolvent at reduced pressure and at the boiling point of the solvent. 8.The process according to claim 7, wherein the reaction is performed at apressure of 10 to 900 mbar.
 9. The process according to claim 8, whereinthe reaction is performed at a pressure of 50 to 500 mbar.
 10. Theprocess according to claim 7, wherein the reaction is performed at atemperature of 0 to 80° C.
 11. The process according to claim 8, whereinthe reaction is performed at a temperature of 0 to 80° C.
 12. Theprocess according to claim 9, wherein the reaction is performed at atemperature of 0 to 80° C.
 13. The process according to claim 10,wherein the temperature is from 20 to 50° C.
 14. The process accordingto claim 11, wherein the temperature is from 20 to 50° C.
 15. Theprocess according to claim 12, wherein the temperature is from 20 to 50°C.
 16. The process according to claim 7, wherein said solvent is analiphatic or aromatic hydrocarbon.
 17. The process according to claim 8,wherein said solvent is an aliphatic or aromatic hydrocarbon.
 18. Theprocess according to claim 9, wherein said solvent is an aliphatic oraromatic hydrocarbon.
 19. The process according to claim 10, whereinsaid solvent is an aliphatic or aromatic hydrocarbon.
 20. The processaccording to claim 11, wherein said solvent is an aliphatic or aromatichydrocarbon.
 21. The process according to claim 12, wherein said solventis an aliphatic or aromatic hydrocarbon.
 22. The process according toclaim 13, wherein said solvent is an aliphatic or aromatic hydrocarbon.23. The process according to claim 14, wherein said solvent is analiphatic or aromatic hydrocarbon.
 24. The process according to claim15, wherein said solvent is an aliphatic or aromatic hydrocarbon. 25.The process according to claim 7, wherein said reduced pressure is belowatmospheric pressure.
 26. The process according to claim 25, whereinsaid reaction is conducted in a vessel.
 27. The process according toclaim 7, wherein said reaction is conducted in a vessel.